Inefficient targeting to the endoplasmic reticulum by the signal recognition particle elicits selective defects in post-ER membrane trafficking
Inefficient targeting to the endoplasmic reticulum by the signal recognition particle elicits selective defects in post-ER membrane trafficking
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DOI：
10.1016/j.yexcr.2006.12.003
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发表时间：
2007-02-15
影响因子：
3.7
通讯作者：
Strub, Katharina
中科院分区：
文献类型：
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作者：
Lakkaraju, Asvin K. K.;Luyet, Pierre-Philippe;Strub, Katharina
信号识别颗粒（SRP）是蛋白质转运到内质网（ER）所必需的。通过RNA干扰，我们将其在哺乳动物细胞中的水平降低了大约10倍，以研究其细胞功能。如此低的水平被证明不足以有效靶向er，因为分泌途径中几种蛋白质的积累被特异性地减少了。虽然细胞看起来没有受到影响，但它们在er后膜运输中表现出明显的选择性缺陷。具体来说，VSV-G的顺行转运和志贺毒素b亚基的逆行转运在高尔基水平上停滞不前，而内吞噬的转铁蛋白受体未能再循环到质膜。内吞膜从质膜到溶酶体或高尔基体的运输未受干扰，内质网和高尔基体的主要形态学变化在低分辨率下无法检测到。选择性膜运输缺陷在低水平SRP足以有效靶向er的条件下被特异性抑制，因此是SRP水平降低的细胞靶向能力较低的直接结果。选择性内质网后膜运输缺陷发生在足以存活的SRP水平上，这表明SRP水平的变化及其对内质网后膜运输的影响可能是暂时改变选定蛋白定位的一种机制。(c) 2006爱思唯尔公司版权所有。
The signal recognition particle (SRP) is required for protein translocation into the endoplasmic reticulum (ER). With RNA interference we reduced its level about ten-fold in mammalian cells to study its cellular functions. Such low levels proved insufficient for efficient ER-targeting, since the accumulation of several proteins in the secretory pathway was specifically diminished. Although the cells looked unaffected, they displayed noticeable and selective defects in post-ER membrane trafficking. Specifically, the anterograde transport of VSV-G and the retrograde transport of the Shiga toxin B-subunit were stalled at the level of the Golgi whereas the endocytosed transferrin receptor failed to recycle to the plasma membrane. Endocytic membrane trafficking from the plasma membrane to lysosomes or Golgi was undisturbed and major morphological changes in the ER and the Golgi were undetectable at low resolution. Selective membrane trafficking defects were specifically suppressed under conditions when low levels of SRP became sufficient for efficient ER-targeting and are therefore a direct consequence of the lower targeting capacity of cells with reduced SRP levels. Selective post-ER membrane trafficking defects occur at SRP levels sufficient for survival suggesting that changes in SRP levels and their effects on post-ER membrane trafficking might serve as a mechanism to alter temporarily the localization of selected proteins. (c) 2006 Elsevier Inc. All rights reserved.